Effect of perfusion rate on the time course of insulin-mediated skeletal muscle glucose uptake
Effect of perfusion rate on the time course of insulin-mediated skeletal muscle glucose uptake
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DOI：
10.1152/ajpendo.1996.271.6.e1067
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发表时间：
1996-12-01
影响因子：
5.1
通讯作者：
Steinberg, HO
中科院分区：
文献类型：
--
作者：
Baron, AD;BrechtelHook, G;Steinberg, HO
为了更好地确定骨骼肌葡萄糖摄取的时间过程及其通过灌注变化的调节，我们进行了全身性正常血糖-高胰岛素钳夹（40 μ l）。m（-2）。min（-1））持续90 min，在一组瘦的胰岛素敏感受试者（n = 9）中进行两次（间隔4周），胰岛素介导的血管舒张功能完好或受到抑制。胰岛素介导的血管舒张被股动脉内输注N-G-单甲基-L-精氨酸（L-NMMA）（一氧化氮合酶的特异性抑制剂）抑制。在研究期间，每10分钟测量腿部血流量（LBF）和动静脉葡萄糖差（AVG Delta）;腿部葡萄糖摄取（LGU）计算为LGU = LBF x AVG Delta。全身胰岛素输注使LBF从0.194 +/- 0.024增加到0.349 +/- 0.046 l/min（P < 0.01）。股动脉灌注L-NMMA完全抑制LBF的这种增加。在两项研究中，AVG Delta、LGU和全身葡萄糖处置率均以时间依赖性方式增加。胰岛素介导的血管舒张完整时的最大AVG Delta低于抑制时的最大AVG Delta（25.9 +/- 2.5 vs. 35.0 +/- 1.6 mg/dl，P < 0.001）。胰岛素介导的血管舒张功能完好时达到半最大AVG Delta（T-1/2）的时间略长于抑制时（35.6 +/- 4.1 vs. 29.7 +/- 1.6 min，P < 0.01）。在完整和抑制胰岛素介导的血管舒张期间，最大LGU分别为93.9 +/- 26.8和57.2 +/- 11.6 mg/min（P < 0.005），T-1/2 LGU分别为50.2 +/- 16.0和36.3 +/- 8.8 min（P = 0.1）。因此，胰岛素介导的血管舒张在减缓胰岛素刺激葡萄糖摄取的时程方面具有适度的作用，但在增加骨骼肌中胰岛素刺激的葡萄糖摄取的最大速率方面具有显著的作用。在原发性高血压患者中观察到的胰岛素介导的血管舒张功能受损可能至少部分解释了这些患者中观察到的胰岛素抵抗。
To better define the time course of skeletal muscle glucose uptake and its modulation by changes in perfusion, we performed systemic euglycemic-hyperinsulinemic clamps (40 mu . m(-2) . min(-1)) for a 90-min period in a group of lean, insulin-sensitive subjects (n = 9) on two occasions (similar to 4 wk apart) with insulin-mediated vasodilation intact or inhibited. Insulin-mediated vasodilation was inhibited by an intrafemoral artery infusion of N-G-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthase. During the study, leg blood flow (LBF) and arteriovenous glucose difference (AVG Delta) were measured every 10 min; leg glucose uptake (LGU) was calculated as LGU = LBF x AVG Delta. The systemic insulin infusion caused a time-dependent increase in LBF from 0.194 +/- 0.024 to 0.349 +/- 0.046 l/min (P < 0.01). The intrafemoral artery infusion of L-NMMA completely inhibited this increase in LBF. AVG Delta, LGU, and whole body glucose disposal rates increased in a time-dependent manner in both studies. The maximum AVG Delta was lower with insulin-mediated vasodilation intact than when inhibited (25.9 +/- 2.5 vs. 35.0 +/- 1.6 mg/dl, P < 0.001). The time to achieve half-maximal (T-1/2) AVG Delta was somewhat longer with insulin-mediated vasodilation intact compared with inhibited (35.6 +/- 4.1 vs. 29.7 +/- 1.6 min, P < 0.01). Maximal LGU was 93.9 +/- 26.8 and 57.2 +/- 11.6 mg/min (P < 0.005), and the T-1/2 LGU was 50.2 +/- 16.0 and 36.3 +/- 8.8 min (P = 0.1) during intact and inhibited insulin-mediated vasodilation, respectively. Thus insulin-mediated vasodilation has a modest effect in slowing the time course at which insulin stimulates glucose uptake but has a marked effect in augmenting the maximal rate of insulin-stimulated glucose uptake in skeletal muscle. Impaired insulin-mediated vasodilation, as observed in patients with essential hypertension, may explain, at least in part, the insulin resistance observed in these patients.